Doing a fully-painted comic strip is very difficult work--most people who do painted comics have to take a long time to put them together, and it's almost impossible to do a monthly painted strip all by yourself. So Kurtzman hired a number of assistants over the years to help lighten the load a bit. Many of those assistants were former Mad artists, including Will Elder, Jack Davis, Russ Heath, Al Jaffee, and others.

The strip, which ran every single month at first, cut back to occasional issues during the 1970s. Playboy cancelled the feature in 1988, with over 100 episodes in the bank. Kurtzman died in 1993, but the older cartoons had always been popular as reprints, so Playboy brought "Little Annie Fanny" back in 1998 with artwork by Ray Lago and Bill Schorr.